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Impact of Structurally Diverse BET Inhibitors on SIRT1

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Item embargoed until 2021-03-10. Restrictions imposed by the publisher
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Date
2020
Author(s)
Tenhunen, Jonna
Kokkola, Tarja
Huovinen, Marjo
Rahnasto-Rilla, Minna
Lahtela-Kakkonen, Maija
Unique identifier
10.1016/j.gene.2020.144558
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Self-archived article

Citation
Tenhunen, Jonna. Kokkola, Tarja. Huovinen, Marjo. Rahnasto-Rilla, Minna. Lahtela-Kakkonen, Maija. (2020). Impact of Structurally Diverse BET Inhibitors on SIRT1.  Gene, 741, 144558. 10.1016/j.gene.2020.144558.
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© 2020 Elsevier B.V.
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CC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
Abstract

The epigenetic regulation of gene expression is controlled by various processes, of which one is histone acetylation. Many proteins control gene expression via histone acetylation. Those proteins include sirtuins (SIRTs) and bromodomain and extraterminal proteins (BETs), which are known to regulate same cellular processes and pathways. The aim of this study was to explore BET inhibitors’ effects on SIRT1. Previously we showed that BET inhibitor (+)-JQ1 increases SIRT1 levels, but in the current study we used also other, structurally diverse BET inhibitors, I-BET151 and Pfi-1, and examined their effects on SIRT1 levels in two breast cancer cell lines. The results differed between the inhibitors and also between the cell lines. (+)-JQ1 had opposite effects on SIRT1 levels in the two cell lines, I-BET151 increased the levels in both cell lines, and Pfi-1 had no effect. In conclusion, the effect of structurally diverse BET inhibitors on SIRT1 levels is divergent, and the responses might also be cell type-dependent. These findings are important for all SIRT1 and BET inhibitor-related research, and they show that different BET inhibitors might have important individual effects.

Subjects
epigenetic regulation   SIRT1   BET inhibitor   
URI
https://erepo.uef.fi/handle/123456789/8137
Link to the original item
http://dx.doi.org/10.1016/j.gene.2020.144558
Publisher
Elsevier BV
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  • Terveystieteiden tiedekunta [1324]
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